(7aR)-1-[(2R,5S,E)-6-Hydroxy-5,6-dimethylhept-3-en-2-yl]-7a-methylhexahydro-1H-inden-4(2H)-one

The chiral title compound, C19H32O2, contains a [4.3.0]-bicyclic moiety in which the shared C—C bond presents a trans configuration and a side chain in which the C=C double bond shows an E conformation. The conformations of five- and six-membered rings are envelope (with the bridgehead atom bearing the methyl substituent as the flap) and chair, respectively, with a dihedral angle of 4.08 (17)° between the idealized planes of the rings. In the crystal, the molecules are self-assembled via classical O—H⋯O hydrogen bonds, forming chains along [112]; these chains are linked by weak non-classical C—H⋯O hydrogen bonds, giving a two-dimensional supramolecular structure parallel to (010). The absolute configuration was established according to the configuration of the starting material.


Marcos L. Rivadulla, Massene Sene, María González and Berta Covelo Comment
The title compound is a precursor of 1α,25-dihydroxyvitamin D3 (calcitriol) analogue which is the hormonally active form of vitamin D3. Besides regulating calcium homeostasis, this form is also involved in other cellular processes such as cell differentiation; immune system regulation and gene transcription (Henry, 2011). Nevertheless, the clinical utility of this hormone for treatment of cancers and skin disorders is limited by its hypercalcemic effects (Heaney, 2008), for this purpose the design and synthesis of more selective biological-effect analogues is of paramount importance. In the title compound ( Figure 1), the C3A-C7A shared bond of the bicyclic moiety presents a trans configuration. Besides, the 5membered ring adopts an envelope conformation with puckering parameters Q = 0.462 (3) Å and φ = 136.5 (4)° and with the bridgehead C7A atom bearing the methyl substituent as the flap (Cremer & Pople, 1975)  the resulting chains are connected by weak non-classical C-H···O hydrogen bonds to create a two-dimensional supramolecular structure (Table 1, Figure 2).

Experimental
Over a stirring solution of inhoffen-lythgoe diol (2.1 g; 7.2 mmol) in CH 2 Cl 2 (10 ml), PDC S-methyl-3-hydroxy-2methylpropionate (5.4 g; 14.4 mmol) was added. The mixture was stirred at room temperature for 16 h then it was quenched with ethylic ether (20 ml) and stirred one more hour. The solid precipitated was filtered over celite, the organic layer was concentrated and the residue was purified by flash column chromatography on silica gel (10% ethyl acetate/hexane) to afford the title compound (1.8 g; 80%). The crystals were obtained by slow evaporation in a closed camera of a solution of the compound in a mixture of ethyl acetate/hexane (7:3).

Refinement
All H-atoms were positioned and refined using a riding model with O-H = 0.82 Å and C-H = 0.98, 0.97, 0.96 and 0.93 Å for methine, methylelne, methyl and vinyl H-atoms, respectively. The H-atoms were allowed U iso = 1.5U eq (O/C-methyl) or 1.2U eq (the rest of the C atoms). Due to insufficient anamolous dispersion effects, an absolute structure was not established in this analysis and 1457 Friedel pairs were not merged. However, the absolute configuration of the title compound was established according to the configuration of starting material.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq C1 0.31315 (